Treatment of Posttraumatic Stress Disorder: An Assessment of the Evidence (2008)

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Committee on Treatment of Posttraumatic Stress Disorder Board on Population Health and Public Health Practice 

THE NATIONAL ACADEMIES PRESS  500 Fifth Street, N.W.  Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Govern- ing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineer- ing, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropri- ate balance. This study was supported by Contract No. V101(93)P-2136, Task Order No. 9, between the National Academy of Sciences and the Department of Veterans Af- fairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number-13:  978-0-309-10926-0 International Standard Book Number-10:  0-309-10926-4 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2008 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent a ­ dopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin. Suggested citation: Institute of Medicine (IOM). 2008. Treatment of posttraumatic stress disorder: An assessment of the evidence. Washington, DC: The National Academies Press. 



The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general wel- fare. Upon the authority of the charter granted to it by the Congress in 1863, the ­ Academy has a ­ mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding e ­ ngineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineer- ing programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is presi- dent of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Insti- tute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sci- ences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org 

COMMITTEE ON TREATMENT OF POSTTRAUMATIC STRESS DISORDER ALFRED O. BERG, M.D., M.P.H., (Chair), Professor, Department of Family Medicine, University of Washington School of Medicine, Seattle NAOMI BRESLAU, Ph.D., Professor, Department of Epidemiology, Michigan State University, East Lansing STEVEN N. GOODMAN, M.D., M.H.S., Ph.D., Associate Professor of Oncology, Pediatrics, Epidemiology, and Biostatistics, Department of Oncology, Division of Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD MURIEL D. LEZAK, Ph.D., Professor Emerita, Neurology, Oregon Health and Science University, School of Medicine, Portland DAVID B. MATCHAR, M.D., Director and Professor of Medicine, Center for Clinical Health Policy Research, Duke University Medical Center, Durham, NC  THOMAS A. MELLMAN, M.D.,* Professor and Vice Chair for Research, Department of Psychiatry, Howard University, Washington, DC DAVID SPIEGEL, M.D., Willson Professor, School of Medicine, Associate Chair, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA WILLIAM A. VEGA, Ph.D., Professor, Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA Study Staff ALINA BACIU, M.P.H., Study Director AMY GELLER, M.P.H., Senior Health Policy Associate MATHEW SOLYST, Project Assistant (through May 2007) DAVID TOLLERUD, Project Assistant (from May 2007) NIDA CORRY, M.S., Christine Mirzayan Science and Technology Policy Fellow and Consultant ROSE MARIE MARTINEZ, Sc.D., Director, Board on Population Health and Public Health Practice   *Dr. Mellman does not concur with the committee’s consensus on two conclusions—on SSRIs and novel antipsychotic medications—and offers alternate conclusions (see Appendix H).  



Reviewers T his report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC’s Report Review Committee. The purpose of this independent review is to provide candid and critical com- ments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: Art Blank, Jr., Psychiatrist, Bethesda, Maryland Gregory Burke, Department of Public Health Sciences, Wake Forest University School of Medicine Allen J. Dietrich, Department of Community and Family Medicine, Dartmouth Medical School and MacArthur Foundation Initiative on Depression and Primary Care at Dartmouth and Duke Ted Ganiats, Department of Family and Preventive Medicine and Health Outcomes Assessment Program (HOAP), University of California, San Diego School of Medicine John E. Halver, School of Aquatic and Fishery Sciences, Professor Emeritus in Nutrition, University of Washington Stevan Hobfoll, The Applied Psychology Center, Kent State University vii 

viii REVIEWERS Donald F. Klein, New York Presbyterian Hospital and Columbia University Department of Psychiatry, Professor Emeritus, New York State Psychiatric Institute, Director of Research Emeritus Roderick J. Little, Department of Biostatistics, University of Michigan Craig Mallinckrodt, Eli Lilly and Company James McNulty, Depressive/Manic Depressive Association of Rhode Island Cynthia Mulrow, Department of Medicine, University of Texas Health Science Center at San Antonio Barbara O. Rothbaum, Department of Psychiatry, Emory University School of Medicine Peter P. Roy-Byrne, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine and Harborview Center for Healthcare Improvement for Addictions, Mental Illness and Medically Vulnerable Populations (CHAMMP), Harborview Medical Center Myrna M. Weissman, College of Physician and Surgeons, Columbia University Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Elaine L. ­Larson, School of Nursing, Columbia University. Appointed by the ­ National ­ Research C ­ ouncil she was responsible for making certain that an independent examina­tion of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Re- sponsibility for the final content of this report rests entirely with the author- ing committee and the institution. 

Preface T his report was commissioned by the Department of Veterans ­Affairs (VA) to assess the scientific evidence on treatment modalities for Post- traumatic Stress Disorder (PTSD). Reviewing the PTSD treatment literature dating back to 1980, the year the disorder was first ­ defined by the Diagnostic and Statistical Manual of the American Psychiatric Asso­cia­ tion, proved to be a challenging task. Assessing the outcomes of treatment depends entirely upon the self-report of those affected, without “objec- tive” measures such as laboratory tests or imaging. Treatment modalities and research methods used in their evaluation have been in continuous development. The last 30 years have also seen dramatic changes in the way scientific evidence has been assessed in general with emerging international standards for conducting systematic qualitative and quantitative reviews that are quite different from the methods used in the 1980s when research on the treatment of PTSD began. In applying a rigorous approach to the assessment of evidence that meets today’s standards, the committee identified significant gaps in the evidence that made it impossible to reach conclusions establishing the e ­ fficacy of most treatment modalities. This result was unexpected and may surprise VA and others interested in the disorder. Important treatment decisions for most modalities will need to be made without a strong body One committee member does not concur with the committee’s specific conclusions concern- ing (a) selective serotonin reuptake inhibitors (SSRIs) and (b) novel antipsychotic medications as add-on treatments, as described in Appendix H; however, that does not affect his agreement with these general statements about the overall inadequacy of the evidence. ix 

 PREFACE of evidence meeting current standards (the committee summarizes clinical practice guidelines developed by others in the face of this scientific uncer- tainty). This overall conclusion of scientific inadequacy is not a clinical practice recommendation or guideline. It is also not a judgment on the qual- ity of the research in this field using methods acceptable at the time. The overall conclusion also adds urgency to the committee’s recommendations for a more strategic research effort that defines the relevant populations and subpopulations; develops and tests treatment modalities alone and in combination, in individual and group formats (for psychotherapy), and of various intensities and durations; uses the latest and most rigorous methods for designing and executing study protocols; and follows all study partici- pants through the end of treatment and for meaningful periods thereafter. The committee was also struck by the scant evidence exploring some of the possibly unique aspects of PTSD in veterans. For the most part we can- not say whether the treatment of PTSD in veterans should be the same as in civilians, and whether important subpopulations of veterans defined by age, sex, trauma type, socioeconomic status, educational level, ­ comorbidities, and brain injury should be treated the same or differently. The committee could only conclude that well-designed research is needed to answer the key questions regarding the efficacy of treatment modalities in veterans. Success will depend on the collaboration of VA and other government agencies, researchers, clinicians, and patient and veter- ans’ groups and will further require the continued support and attention of policymakers and the public. The individuals returning from current con- flicts and now re-entering civilian life with this disorder deserve no less. Alfred O. Berg Chair 

Contents Summary 1 1 Introduction 17 The Study Process, 19 The Disorder, 21 PTSD in the Veteran Population, 24 Treatment of Patients with PTSD, 25 Summary of the Major Clinical Practice Guidelines, 31 Summation, 34 References, 34 2 Methods 39 The Literature Search, 39 Reaching Conclusions Regarding the Efficacy of Treatment Modalities, 42 Summary of the Literature Reviewed in Making Conclusions, 46 Summary of Existing Systematic Reviews and Meta-Analyses, 46 Evaluating the Evidence, 51 References, 51 3 Evidence and Conclusions: Pharmacotherapy 55 Alpha-Adrenergic Blockers, 56 Anticonvulsants, 57 Novel Antipsychotic Medications, 59 Benzodiazepines, 62 xi 

xii CONTENTS Monoamine Oxidase Inhibitors, 63 Selective Serotonin Reuptake Inhibitors, 67 Other Antidepressants, 78 Other Drugs, 79 Summation, 85 References, 85 4 Evidence and Conclusions: Psychotherapy 93 Exposure Therapies, 95 Eye Movement Desensitization and Reprocessing, 99 Cognitive Restructuring, 113 Coping Skills Therapies, 118 Other Psychotherapies, 122 Group Therapy, 124 Summation, 127 References, 128 5 Issues in PTSD Treatment Research 137 Issues Identified in Reviewing the Evidence, 137 Issues Defined in the Statement of Task, 146 Concluding Observations, 154 References, 155 Appendixes A PTSD Psychological Interventions 159 B Search Strategy 165 C Measures Used in the Assessment of Posttraumatic Stress Disorder 169 D Analysis and Interpretation of Studies with Missing Data 185 E Acronyms 195 F Agenda for Public Meeting Held by the Committee on Treatment of PTSD 199 G Committee Member Biographies 203 H Minority Opinion of Dr. Thomas Mellman 209